CA2217601C - Composes de benzimidazole et leur utilisation en tant que modulateurs du complexe de recepteurs gabaa - Google Patents
Composes de benzimidazole et leur utilisation en tant que modulateurs du complexe de recepteurs gabaa Download PDFInfo
- Publication number
- CA2217601C CA2217601C CA002217601A CA2217601A CA2217601C CA 2217601 C CA2217601 C CA 2217601C CA 002217601 A CA002217601 A CA 002217601A CA 2217601 A CA2217601 A CA 2217601A CA 2217601 C CA2217601 C CA 2217601C
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- Prior art keywords
- compound
- alkyl
- pyrrolyl
- phenyl
- disorder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims abstract description 4
- 102000027484 GABAA receptors Human genes 0.000 title claims description 25
- 108091008681 GABAA receptors Proteins 0.000 title claims description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 208000035475 disorder Diseases 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 10
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 8
- 208000026139 Memory disease Diseases 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 230000036506 anxiety Effects 0.000 claims abstract description 8
- 208000019116 sleep disease Diseases 0.000 claims abstract description 8
- 206010010904 Convulsion Diseases 0.000 claims abstract description 7
- 125000002252 acyl group Chemical group 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 5
- 206010015037 epilepsy Diseases 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- -1 2,5-dimethyl-1-pyrrolyl Chemical group 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 10
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- UYNZVZFXQKFDED-UHFFFAOYSA-N 1-(3-pyridin-3-ylphenyl)-5-pyrrol-1-ylbenzimidazole Chemical compound C1=CC=CN1C1=CC=C(N(C=N2)C=3C=C(C=CC=3)C=3C=NC=CC=3)C2=C1 UYNZVZFXQKFDED-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- WWXZTWMJHKFVCB-UHFFFAOYSA-N 1-(3-pyridin-2-ylphenyl)-5-pyrrol-1-ylbenzimidazole Chemical compound C1=CC=CN1C1=CC=C(N(C=N2)C=3C=C(C=CC=3)C=3N=CC=CC=3)C2=C1 WWXZTWMJHKFVCB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 2
- 125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 claims description 2
- 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 claims description 2
- 125000004507 1,2,5-oxadiazol-3-yl group Chemical group O1N=C(C=N1)* 0.000 claims description 2
- 125000004508 1,2,5-oxadiazol-4-yl group Chemical group O1N=CC(=N1)* 0.000 claims description 2
- 125000004518 1,2,5-thiadiazol-3-yl group Chemical group S1N=C(C=N1)* 0.000 claims description 2
- 125000004519 1,2,5-thiadiazol-4-yl group Chemical group S1N=CC(=N1)* 0.000 claims description 2
- JGJHDTDDLAEWQS-UHFFFAOYSA-N 1-(3-pyrimidin-5-ylphenyl)-5-pyrrol-1-ylbenzimidazole Chemical compound C1=CC=CN1C1=CC=C(N(C=N2)C=3C=C(C=CC=3)C=3C=NC=NC=3)C2=C1 JGJHDTDDLAEWQS-UHFFFAOYSA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 claims description 2
- 125000004500 isothiazol-4-yl group Chemical group S1N=CC(=C1)* 0.000 claims description 2
- 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 claims description 2
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 2
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 2
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 2
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 2
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 2
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 2
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 2
- AYBOURRWLWFCHO-UHFFFAOYSA-N 1-(3-imidazol-1-ylphenyl)-5-pyrrol-1-ylbenzimidazole Chemical compound C1=CC=CN1C1=CC=C(N(C=N2)C=3C=C(C=CC=3)N3C=NC=C3)C2=C1 AYBOURRWLWFCHO-UHFFFAOYSA-N 0.000 claims 1
- RWESIYUZKPABFK-UHFFFAOYSA-N 5-(2,5-dimethylpyrrol-1-yl)-1-(3-imidazol-1-ylphenyl)benzimidazole Chemical compound CC1=CC=C(C)N1C1=CC=C(N(C=N2)C=3C=C(C=CC=3)N3C=NC=C3)C2=C1 RWESIYUZKPABFK-UHFFFAOYSA-N 0.000 claims 1
- JYZIHLWOWKMNNX-UHFFFAOYSA-N benzimidazole Chemical compound C1=C[CH]C2=NC=NC2=C1 JYZIHLWOWKMNNX-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 59
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 238000000034 method Methods 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 238000009472 formulation Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 102000004300 GABA-A Receptors Human genes 0.000 description 9
- 108090000839 GABA-A Receptors Proteins 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 150000001556 benzimidazoles Chemical class 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 208000015114 central nervous system disease Diseases 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007937 lozenge Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
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- 239000007921 spray Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- DZEIKJMNXHOFHL-UHFFFAOYSA-N 3-pyrimidin-5-ylaniline Chemical compound NC1=CC=CC(C=2C=NC=NC=2)=C1 DZEIKJMNXHOFHL-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
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- 239000002270 dispersing agent Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- MNTSPOOCRZDNMT-UHFFFAOYSA-N n-(3-imidazol-1-ylphenyl)acetamide Chemical compound CC(=O)NC1=CC=CC(N2C=NC=C2)=C1 MNTSPOOCRZDNMT-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
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- 238000010992 reflux Methods 0.000 description 3
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- 210000001519 tissue Anatomy 0.000 description 3
- NUIYHMRBFZOEES-UHFFFAOYSA-N 1-(3-nitrophenyl)imidazole Chemical compound [O-][N+](=O)C1=CC=CC(N2C=NC=C2)=C1 NUIYHMRBFZOEES-UHFFFAOYSA-N 0.000 description 2
- LDJQARUUVXLBMV-UHFFFAOYSA-N 1-(4-fluoro-3-nitrophenyl)-2,5-dimethylpyrrole Chemical compound CC1=CC=C(C)N1C1=CC=C(F)C([N+]([O-])=O)=C1 LDJQARUUVXLBMV-UHFFFAOYSA-N 0.000 description 2
- NBGNRDHMSULJBR-UHFFFAOYSA-N 1-(4-fluoro-3-nitrophenyl)pyrrole Chemical compound C1=C(F)C([N+](=O)[O-])=CC(N2C=CC=C2)=C1 NBGNRDHMSULJBR-UHFFFAOYSA-N 0.000 description 2
- JZKYAYMHIJWCGS-UHFFFAOYSA-N 1-n-(3-imidazol-1-ylphenyl)-4-pyrrol-1-ylbenzene-1,2-diamine Chemical compound NC1=CC(N2C=CC=C2)=CC=C1NC(C=1)=CC=CC=1N1C=CN=C1 JZKYAYMHIJWCGS-UHFFFAOYSA-N 0.000 description 2
- GUVANGLCEGPSCH-UHFFFAOYSA-N 1-n-(3-pyridin-2-ylphenyl)-4-pyrrol-1-ylbenzene-1,2-diamine Chemical compound NC1=CC(N2C=CC=C2)=CC=C1NC(C=1)=CC=CC=1C1=CC=CC=N1 GUVANGLCEGPSCH-UHFFFAOYSA-N 0.000 description 2
- XDJYKTBIGSLFJQ-UHFFFAOYSA-N 1-n-(3-pyrimidin-5-ylphenyl)-4-pyrrol-1-ylbenzene-1,2-diamine Chemical compound NC1=CC(N2C=CC=C2)=CC=C1NC(C=1)=CC=CC=1C1=CN=CN=C1 XDJYKTBIGSLFJQ-UHFFFAOYSA-N 0.000 description 2
- OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 2
- JVKJLZRWXBUBFN-UHFFFAOYSA-N 3-imidazol-1-ylaniline Chemical compound NC1=CC=CC(N2C=NC=C2)=C1 JVKJLZRWXBUBFN-UHFFFAOYSA-N 0.000 description 2
- YLNMGMIEOWFPRX-UHFFFAOYSA-N 3-pyridin-2-ylaniline Chemical compound NC1=CC=CC(C=2N=CC=CC=2)=C1 YLNMGMIEOWFPRX-UHFFFAOYSA-N 0.000 description 2
- YTJQJGKMRLQBJP-UHFFFAOYSA-N 3-pyridin-3-ylaniline Chemical compound NC1=CC=CC(C=2C=NC=CC=2)=C1 YTJQJGKMRLQBJP-UHFFFAOYSA-N 0.000 description 2
- LLIOADBCFIXIEU-UHFFFAOYSA-N 4-fluoro-3-nitroaniline Chemical compound NC1=CC=C(F)C([N+]([O-])=O)=C1 LLIOADBCFIXIEU-UHFFFAOYSA-N 0.000 description 2
- GFANQAYLAJNBQR-UHFFFAOYSA-N 5-(3-aminophenyl)-n,n-dimethylpyrimidin-2-amine Chemical compound C1=NC(N(C)C)=NC=C1C1=CC=CC(N)=C1 GFANQAYLAJNBQR-UHFFFAOYSA-N 0.000 description 2
- NYMYGNLCILQUMT-UHFFFAOYSA-N 5-bromo-n,n-dimethylpyrimidin-2-amine Chemical compound CN(C)C1=NC=C(Br)C=N1 NYMYGNLCILQUMT-UHFFFAOYSA-N 0.000 description 2
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- 210000003928 nasal cavity Anatomy 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000216 proconvulsive effect Effects 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229940048181 sodium sulfide nonahydrate Drugs 0.000 description 1
- WMDLZMCDBSJMTM-UHFFFAOYSA-M sodium;sulfanide;nonahydrate Chemical compound O.O.O.O.O.O.O.O.O.[Na+].[SH-] WMDLZMCDBSJMTM-UHFFFAOYSA-M 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D521/00—Heterocyclic compounds containing unspecified hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
La présente invention décrit des composés de formule (I) ou un de leurs sels pharmaceutiquement acceptables ou un de leurs oxydes, dans laquelle R<3> est représentée par la formule (II) dans laquelle A, B et D représentent chacun CH, ou un ou deux des éléments A, B et D représentent N et les autres représentent CH; R<11> représentent phényle, benzimidazolyle, ou hétéroaryle monocyclique, chacun d'eux pouvant être substitué une ou plusieurs fois par des substituants choisis parmi alkyle, halogène, CF3, amino, nitro, cyano, acylamino, alcoxy, acyle, phényle et hétéroaryle monocyclique; et l'un parmi R<6> et R<7> représente hydrogène et l'autre représente pyrrolyle pouvant être substitué une ou plusieurs fois par des substituants choisis parmi halogène, alkyle, phényle et alcoxy. Les composés sont utilisés dans le traitement de troubles variés du système nerveux central, tels que l'épilepsie et autres troubles convulsifs, l'angoisse, les troubles du sommeil et de la mémoire.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK46095 | 1995-04-21 | ||
| DK0460/95 | 1995-04-21 | ||
| PCT/EP1996/001654 WO1996033192A1 (fr) | 1995-04-21 | 1996-04-19 | Composes de benzimidazole et leur utilisation en tant que modulateurs du complexe de recepteurs gaba¿a? |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2217601A1 CA2217601A1 (fr) | 1996-10-24 |
| CA2217601C true CA2217601C (fr) | 2002-04-16 |
Family
ID=8093808
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002218493A Expired - Fee Related CA2218493C (fr) | 1995-04-21 | 1996-04-17 | Composes de benzimidazole et leur utilisation en tant que modulateurs du complexe de recepteurs gabaa |
| CA002217601A Expired - Fee Related CA2217601C (fr) | 1995-04-21 | 1996-04-19 | Composes de benzimidazole et leur utilisation en tant que modulateurs du complexe de recepteurs gabaa |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002218493A Expired - Fee Related CA2218493C (fr) | 1995-04-21 | 1996-04-17 | Composes de benzimidazole et leur utilisation en tant que modulateurs du complexe de recepteurs gabaa |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5922724A (fr) |
| EP (3) | EP1164134A1 (fr) |
| JP (2) | JP3342874B2 (fr) |
| KR (2) | KR100297445B1 (fr) |
| CN (2) | CN1072669C (fr) |
| AT (2) | ATE210132T1 (fr) |
| AU (2) | AU695957B2 (fr) |
| BR (1) | BR9608048A (fr) |
| CA (2) | CA2218493C (fr) |
| CZ (1) | CZ287545B6 (fr) |
| DE (2) | DE69617665T2 (fr) |
| EE (1) | EE04310B1 (fr) |
| HU (1) | HUP9801692A3 (fr) |
| IS (1) | IS1959B (fr) |
| NO (1) | NO314504B1 (fr) |
| NZ (1) | NZ307521A (fr) |
| PL (1) | PL183853B1 (fr) |
| RU (1) | RU2135493C1 (fr) |
| SK (1) | SK282425B6 (fr) |
| TR (1) | TR199701218T2 (fr) |
| UA (1) | UA54393C2 (fr) |
| WO (2) | WO1996033194A1 (fr) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998017651A1 (fr) * | 1996-10-21 | 1998-04-30 | Neurosearch A/S | Composes 1-phenyl-benzimidazole et leur utilisation comme modulateurs du recepteur baga-¿a? |
| GB9622370D0 (en) | 1996-10-28 | 1997-01-08 | Merck Sharp & Dohme | Therapeutic agents |
| GB9702524D0 (en) * | 1997-02-07 | 1997-03-26 | Merck Sharp & Dohme | Therapeutic agents |
| US6162804A (en) * | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6465484B1 (en) | 1997-09-26 | 2002-10-15 | Merck & Co., Inc. | Angiogenesis inhibitors |
| WO2000025780A1 (fr) * | 1998-10-29 | 2000-05-11 | Bristol-Myers Squibb Company | Composes derives d'un noyau amine inhibiteurs de l'enzyme impdh |
| WO2000028991A1 (fr) | 1998-11-13 | 2000-05-25 | Fujisawa Pharmaceutical Co., Ltd. | Remedes contre le syndrome des ovaires polykystiques |
| WO2000059905A1 (fr) * | 1999-04-02 | 2000-10-12 | Neurogen Corporation | Derives aminoalkylimidazole fusionnes aryle et heteroaryle: modulateurs selectifs de recepteurs gabaa |
| US6358949B1 (en) | 1999-04-02 | 2002-03-19 | Neurogen Corporation | Aryl and hetroaryl fused aminoalkyl-imidazole derivatives: selective modulators of bradykinin B2 receptors |
| US6380210B1 (en) | 1999-04-02 | 2002-04-30 | Neurogen Corporation | Heteroaryl fused aminoalkyl-imidazole derivatives: selective modulators of GABAa receptors |
| US6627624B1 (en) | 1999-04-02 | 2003-09-30 | Neurogen Corporation | Aryl fused aminoalkyl-imidazole derivatives: selective modulators of GABAa receptors |
| US6271241B1 (en) | 1999-04-02 | 2001-08-07 | Neurogen Corporation | Cycloalkyl and aryl fused aminoalkyl-imidazole derivatives: modulators and GLP-1 receptors |
| US6281237B1 (en) | 1999-04-02 | 2001-08-28 | Neurogen Corporation | N-phenyl benzimidazolecarboxamide and N-phenyl indolecarboxamide derivatives |
| IL146403A0 (en) | 1999-06-22 | 2002-07-25 | Neurosearch As | Novel benzimidazole derivatives and pharmaceutical compositions comprising these compounds |
| EP1206260A4 (fr) * | 1999-06-30 | 2002-10-30 | Merck & Co Inc | Composes inhibiteurs de la src kinase |
| EP1194152A4 (fr) | 1999-06-30 | 2002-11-06 | Merck & Co Inc | Composes inhibiteurs de la kinase src |
| WO2001000213A1 (fr) * | 1999-06-30 | 2001-01-04 | Merck & Co., Inc. | Composes inhibiteurs de la src kinase |
| KR100875222B1 (ko) * | 1999-08-19 | 2008-12-19 | 아스트라제네카 아베 | 헤테로폴리사이클릭 화합물 및 간접 글루타메이트 수용체길항제로서의 그들의 용도 |
| US6660753B2 (en) * | 1999-08-19 | 2003-12-09 | Nps Pharmaceuticals, Inc. | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| PA8535601A1 (es) * | 2000-12-21 | 2002-11-28 | Pfizer | Derivados benzimidazol y piridilimidazol como ligandos para gabaa |
| GB0208394D0 (en) * | 2002-04-11 | 2002-05-22 | Merck Sharp & Dohme | Therapeutic agents |
| WO2004069160A2 (fr) * | 2003-01-28 | 2004-08-19 | Smithkline Beecham Corporation | Composes chimiques |
| DE602004011914T2 (de) | 2003-04-03 | 2008-06-12 | Neurosearch A/S | Benzimidazole derivate und ihre anwendung als gaba a rezeptor komplex modulatoren |
| EP1613618A2 (fr) | 2003-04-03 | 2006-01-11 | Neurosearch A/S | Derives de benzimidazole et leur utilisation pour moduler le complexe du recepteur gaba sb a /sb |
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| WO1979000936A1 (fr) * | 1978-04-17 | 1979-11-15 | Basab Materialhantering Ab | Dispositif de levage et de transport de marchandises |
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| US5554630A (en) * | 1993-03-24 | 1996-09-10 | Neurosearch A/S | Benzimidazole compounds |
-
1996
- 1996-04-17 PL PL96322892A patent/PL183853B1/pl not_active IP Right Cessation
- 1996-04-17 EP EP01112476A patent/EP1164134A1/fr not_active Withdrawn
- 1996-04-17 AU AU56891/96A patent/AU695957B2/en not_active Ceased
- 1996-04-17 BR BR9608048-5A patent/BR9608048A/pt not_active IP Right Cessation
- 1996-04-17 RU RU97119173A patent/RU2135493C1/ru not_active IP Right Cessation
- 1996-04-17 EP EP96914932A patent/EP0821684B1/fr not_active Expired - Lifetime
- 1996-04-17 UA UA97115591A patent/UA54393C2/uk unknown
- 1996-04-17 SK SK1399-97A patent/SK282425B6/sk unknown
- 1996-04-17 WO PCT/EP1996/001606 patent/WO1996033194A1/fr not_active Ceased
- 1996-04-17 CN CN96193419A patent/CN1072669C/zh not_active Expired - Fee Related
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- 1996-04-17 CA CA002218493A patent/CA2218493C/fr not_active Expired - Fee Related
- 1996-04-17 AT AT96914932T patent/ATE210132T1/de not_active IP Right Cessation
- 1996-04-17 TR TR97/01218T patent/TR199701218T2/xx unknown
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- 1996-04-17 US US08/945,023 patent/US5922724A/en not_active Expired - Lifetime
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- 1996-04-19 CA CA002217601A patent/CA2217601C/fr not_active Expired - Fee Related
- 1996-04-19 JP JP8531487A patent/JP3040485B2/ja not_active Expired - Fee Related
- 1996-04-19 US US08/930,216 patent/US5902813A/en not_active Expired - Lifetime
- 1996-04-19 DE DE69636670T patent/DE69636670T2/de not_active Expired - Lifetime
- 1996-04-19 EP EP96912025A patent/EP0821683B1/fr not_active Expired - Lifetime
- 1996-04-19 AU AU55014/96A patent/AU5501496A/en not_active Abandoned
- 1996-04-19 KR KR1019970707464A patent/KR19990007941A/ko not_active Abandoned
- 1996-04-19 CN CN96193420A patent/CN1182426A/zh active Pending
- 1996-04-19 WO PCT/EP1996/001654 patent/WO1996033192A1/fr not_active Ceased
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